Adult human liver slice cultures: Modelling of liver fibrosis and evaluation of new anti-fibrotic drugs

Figure 4 Viability of human non-fibrotic (F0-F1), and fibrotic (F2-F3, F4) non-infected or hepatitis C virus-infected liver slices during the different kinetic studies, with no treatment cytotoxicity as shown by ATP and LDH dosages. A: Percentage of ATP synthesis/total protein in non-infected (NINF) liver slice (LS) with F0-F1 to F4 stage fibrosis during the 21 days-follow up kinetics; B: The percentage of LDH release/control in NINF LS with a F0-F1 to F4 stage fibrosis during the 21d-follow up kinetics (d: days); C and D: The percentage of ATP synthesis /total protein in F0-F1 NINF and hepatitis C virus (HCV)-infected (INF) LS treated with 1 mmol/L, 5 mmol/L and 25 mmol/L of EtOH during the 21d-follow up kinetics; E: The percentage of ATP synthesis / total protein in the presence of 25 mmol/L of EtOH on F0-F1 NINF and INF LS during the 21d-follow up kinetics; F: LDH release (% of control) in F0-F1 non-infected LS cultures treated or non-treated with 25 mmol/L of EtOH compared to F4 non-infected treated or non-treated with 25 mmol/L of EtOH during the 21d-follow up kinetics. Values are expressed as means ± standard errors (SEMs), (n = 5). ^aP < 0.0001 time factor; ^bP < 0.01 fibrosis stage; ^cP < 0.05 fibrosis stage; ^dP < 0.05 alcohol factor; ⁱP < 0.01 subject vs control (non-treated) (two-way ANOVA test).There is no significant toxic effect of EtOH (25 mmol/L) on F0-F1 NINF and INF LS and F2-F3, F4 NINF LS; G: The percentage of ATP synthesis/total protein during the 21-follow up kinetics showing the viability of F0-F1 NINF or INF LS cultures with or without the presence of palmitate (500 µmol/L); H and I: Absence of drug cytotoxicity (LDH release, (% of control) ) on the viability of human F0-F4 LS NINF or infected (INF) by HCVcc Con1/C3 during the treatment with either UCDA (UA) or Toco or both for 21 days. It is important to note that under 150%, there is no cytotoxic effect of the drugs on LS viability. Values are expressed as means ± SEMs, (n = 5); J and K: The percentage of ATP synthesis / total protein during the 21 days follow up kinetics, in F0-F1 to F4 NINF or infected (INF) LS with combined treatment [Toco + UCDA (UA)]. Values are expressed as means ± SEMs, (n = 5); Levels of significance are as follows between: Subject vs control, ^kP < 0.0001; ^jP < 0.001; ⁱP < 0.01; ^hP < 0.05) (two-way ANOVA test).